Knockdown Of Coup-Tfii Inhibits Cell Proliferation And Induces Apoptosis Through Upregulating Brca1 In Renal Cell Carcinoma Cells

INTERNATIONAL JOURNAL OF CANCER(2016)

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摘要
COUP-TFII belongs to the nuclear receptor family, which is highly expressed in many kinds of tumors. Previous studies have shown that COUP-TFII can promote tumor progression through regulating tumor angiogenesis and cell proliferation and migration of certain cancer cells. However, the function of COUP-TFII in renal cell carcinoma (RCC) is not clear. Here, we showed that clinical RCC tumor tissues showed much higher COUP-TFII expression level than adjacent normal tissues. When COUP-TFII was knocked down in RCC 769-P and 786-O cells by siRNA or shRNA-expressing lentivirus, the cell proliferation was markedly inhibited, and apoptosis increased. Moreover, the tumor growth of COUP-TFII knockdown 769-P and 786-O xenografts in nude mice was also obviously inhibited. Using qRT-PCR and Western blot, we showed that the expression of the tumor suppressor gene BRCA1 was upregulated in COUP-TFII knockdown cells. Simultaneously knockdown of BRCA1 and COUP-TFII partially rescued the inhibited cell proliferation and increased apoptosis in COUP-TFII single knockdown cells. These results indicate that COUP-TFII may play an oncogenic role in RCC, and COUP-TFII may promote tumor progression through inhibiting BRCA1.What's new? The chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is highly expressed in many tumors. While COUP-TFII can promote tumor progression through regulating tumor angiogenesis and cancer cell proliferation and migration in certain tumors, its function in renal cell carcinoma (RCC) remains unclear. Here, the authors report that COUP-TFII-knockdown RCC cells show inhibited cell proliferation and increased apoptosis. Overall, the results indicate that COUP-TFII may play an oncogenic role in RCC and possibly promote tumor progression through inhibiting BRCA1. COUP-TFII thus offers potential both as a new biomarker for the diagnosis and a new target for the therapy of RCC.
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关键词
COUP-TFII, renal cell carcinoma, BRCA1, cell proliferation, apoptosis
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